Total synthesis and biological assessment of benzimidazole-based analogues of epothilone A: Ambivalent effects on cancer cell growth inhibition

被引：29

作者：

Cachoux, F

Isarno, T

Wartmann, M

Altmann, KH

机构：

[1] ETH Honggerberg, ETH Zurich, Dept Chem & Appl Biosci, Inst Pharmaceut Sci, CH-8093 Zurich, Switzerland

[2] Novartis Inst Biomed Res, Oncol DA, Basel, Switzerland

来源：

CHEMBIOCHEM | 2006年 / 7卷 / 01期

关键词：

antitumor agents; drug discovery; epothilones; microtubule stabilizer; natural products; total synthesis;

D O I：

10.1002/cbic.200500351

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Benzimidazole-based analogues of cis- and trans-Epo A, 2 and 3, have been prepared through stereoselective total synthesis. Both compounds are highly potent antiproliferative agents, but the effects of side-chain replacement on cellular activity are ambivalent. While significantly enhanced potency is observed against a drug-sensitive human cancer cell line, 2 and 3 more susceptible to P-gp-mediated drug efflux than Epo A or frans-Epo A. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

页码：54 / 57

页数：4

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